Oral manifestation of Systemic Drugs

Many commonly prescribed medications are capable of causing adverse drug reactions. It is important for the dentist to have knowledge about these reactions to arrive at a proper diagnosis.

Effects of Drugs on Oral Mucosa and Tongue

Oral mucosal membranes may be the sole site of involvement or they may be a part of a more generalised skin reaction to the offending drug. The main type of hypersensitivity reaction that affects oral mucosa is a delayed reaction mediated by sensitized T- lymphocyte. Stomatitis medicamentosa or fixed drug eruption, occurs with systemic drug usage and stomatitis venenata appears with contact hypersensitivity. Lesions associated with fixed drug eruption are erythematous in mild cases and appear ulcerated in severe cases. The reactions usually appear in 24 hours post- ingestion of the drug. Delayed reaction (up to two weeks) has been noted after use of ampicillin. Withdrawal of the causative drug results in resolution of the lesions.

Contact stomatitis

Contact stomatitis is a local reaction of the mucosa after repeated contact with the causative agent. Reactions can be seen as erythematous to ulcerative lesions. The patient may complain of a burning sensation in the mouth together with xerostomia. The reaction may develop from days to years post-exposure to the causative agent.

Aphthous Stomatitis

Aphthous stomatitis (canker sores) is commonly observed and is mediated by the immune system. Lesions usually appear as painful, tiny, discrete or grouped papules and vesicles. These lesions are small in diameter with round, shallow ulcerations predominantly seen over the labial and buccal mucosa. The reactions heal without scarring in 10-14 days, however, recurrence is common.

Burning Mouth Syndrome

This syndrome may occur due to psychogenic factors, hormonal withdrawal, folate, iron, pyridoxine deficiency or hypersensitivity reactions to the materials utilised in dental prosthesis. The mechanism of ACE-inhibitor “scalded mouth” is uncertain, but it may be a subclinical manifestation of lichen planus.

Glossitis

Glossitis is inflammation of the tongue that is characterised by swelling and intense pain that may be referred to the ear area. Salivation, fever and enlarged regional lymph nodes may develop during an infectious disease or after a burn or other injury.

Erythema Multiforme (Stevens–Johnson Syndrome)

Erythema muultiforme, in severe cases termed as Stevens–Johnson Syndrome, is a mucocutaneous disorder characterised by various clinical types of lesions. Young male adults are predominantly affected. The lips are swollen, crusted and bleed. Widespread erythema can be seen within the mouth. The oral lesions disappear within 14 days of drug withdrawal. Only 4% of erythema reactions are caused by drugs, however, 80% of cases occur in Stevens– Johnson Syndrome.

Oral Ulceration

A number of chemicals used by dental surgeons can cause “burns” of the oral mucosa, i.e. trichloroacetic acid used in the treatment of pericoronitis.

Vesiculo–Bullous Lesions

The exact mechanism of this reaction is unclear, but it seems to be the consequence of a direct irritant effect. Patients using steroid inhalers for more than 5 years are more prone to the development of oral blistering. This type of reaction has also been reported for naproxen and penicillamine.

Lichenoid Eruptions

Unlike true lichen planus, drug-induced lichenoid eruptions disappear after drug withdrawal. Lichenoid drug eruptions rarely affect the buccal mucosa. A characteristic white lace pattern may be present. It is thought that drugs causing lichenoid reactions only uncover the latent disease of lichen planus or amplify a previous disorder, rather than inducing the disease de novo.

Colour Changes of Oral Mucosa and Teeth

Discolouration can occur after direct contact with or following systemic absorption of a drug. Historically, exposure to metals like silver, bismuth, gold, lead, mercury, zinc and copper were the main causative agents of tissue discolouration. Colour changes are typically seen along the gingival margins and are caused by the formation of metallic sulphides as a result of reactions with plaque products in gingival pockets.

Black Hairy Tongue (Lingua villosa nigra)

In this condition there is an elongation of the filiform papillae of the tongue to form hair-like overgrowth that becomes stained brown or black due to proliferation of chromogenic microorganisms. Black hairy tongue can be seen with the administration of oral antibiotics, poor dental hygiene and excessive smoking in adults.

Postmortem Pink–Red Coloration

Tooth colouration of this nature is due to hemolysis and exudation of hemoglobin to dental pulp and is enhanced in the presence of moisture and increased venous pressure. Specific conditions of death associated with this phenomenon include drowning, aspiration pneumonitis and suffocation. Overdoses with barbiturates and carbon monoxide also demonstrate similar findings.

Effects of Drugs on Gingiva and Salivary glands

Drug Induced Gingival Hyperplasia

The growth starts as a painless, beadlike enlargement of the interdental papilla and extends to the facial and lingual gingival margin. The enlargement is usually generalised throughout the mouth but is more severe in the maxillary and mandibular anterior regions. Plaque removal and good oral hygiene may benefit in a fast recovery and limits the severity of the lesion but the lesion does not get completely cured. It is hypothesized that in noninflamed gingiva, fibroblasts are less active or even quiescent and do not respond to circulating drugs; fibroblasts within inflamed tissue are in an active state as a result of inflammatory mediators and the endogenous growth factors.

Salivary Glands

The salivary glands are under control of the autonomic nervous system, mainly the parasympathetic division. Salivary gland function can be affected by a variety of drugs that can produce xerostomia.

Altered salivary flow rate and levels of secretory proteins or enzymes may cause destructive effects on oral and dental health and wound healing. Systemic drug therapy can also produce pain and swelling of the salivary glands.

Muscular and Neurological Disorders and Taste Disturbance

Taste Disturbance

Many drugs induce abnormalities of taste by processes not yet fully understood. The alteration in taste may be simply a blunting or decreased sensitivity in taste perception (hypogeusia), a total loss of the ability to taste (ageusia) or a distortion in perception of the correct taste of a substance for example, sour or sweet (dysgeusia). A wide range of drugs give rise to dysgeusia or hypogeusia either by interfering in chemical composition or flow of saliva or more specifically, affecting taste receptor function or signal transduction. Sulfhydryl compounds are a common cause of taste disturbance. Drugs with the potential for affecting taste are listed below.

Oral Infections Induced or Aggravated by Drugs

Many types of systemic drug therapy can alter oral flora and therefore, predispose the mouth to bacterial or fungal infection. Drugs that have been implicated in this problem include corticosteroids, antimicrobials, anticancer drugs, immunosuppressive agents and oral contraceptives. Drugs causing xerostomia may also potentiate the initiation of oral infections.

Facial Edema/Angioedema

Facial edema is often a manifestation of drug induced hypersensitivity reactions and angiotensin converting enzyme inhibitors (ACEIs) are the most common cause. It seems that angioedema arises as a consequence of an alternation in bradykinin metabolism in susceptible patients. The most common ACEIs implicated in this reaction are captopril, lisinopril and enalapril. Angioedema usually occurs within hours or at most weeks after starting the ACEI and reverses within hours of stopping. However, it can develop after longterm therapy.

Stomatodynia

Stomatodynia is pain in the mouth and can be a consequence of drug reactions.

Cheilitis

Cheilitis is an abnormal condition of the lips characterized by inflammation and cracking of the skin.